The entero-pancreatic peptides, cholecystokinin (CCK) and glucagon, are thought to constitute hormonal signals for suppression of feeding (satiety). Although the vagus nerves appear to be involved in CCK- and glucagon-induced satiety, the peripheral and central neural substrates which mediate the ingestive effects of these peptides have not been studied in detail. For example, we do not know which population of vagal fibers are necessary for expression of CCK- or glucagon-induced satiety. Furthermore, the brain areas through which the vagus exerts its effects on ingestion have not been identified, nor has any specific vagal transmitter substance been associated with neurons mediating the satiety effects of CCK or glucagon. The experiments proposed in this application will use novel neurotoxins (capsaicin and alloxan) in combination with ablation techniques to identify the vaga sensory fibers and brain projections which mediate CCK- and glucagon-induced satiety. In addition, these experiments will attempt to determine whether specific peptidergic neurotransmitters are involved in mediating the satiety effects of these peptides. The results should provide a means to examine the importance of these satiety signals in normal appetite and appetite disorders. Furthermore, pharmacological characterization of the vagal neurons which carry satiety signals may permit the development of drugs through which these signals may be manipulated